Neuropathies Flashcards
Guillain-Barre Syndrome
Background and epidemiology
- Inflammatory, immune-mediated disease of PNS (peripheral nerves and nerve roots)
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Typical presentation:
-Acute onset weakness & sensory symptoms in the lower limbs that ascend to involve the upper limbs and cranial nerves - Most common cause of acute flaccid paralysis
- All age froups affected, incidence increases with increasing age
- Slightly > men
- Lifetime risk 1/1000
- **Subtypes (electrophysiology)
- **Acute inflammatory demyelinating polyradiculopathy (AIDP)
- Acute motor axonal neuropathy (AMAN)
- Acute motor sensory axonal neuropathy (AMSAN)
- **Clinical subtypes
- **See attached photo
GBS
Clinical features
> 95% monophasic course
**2/3rds antecedant respiratory or diarrhoeal illness 4-6 weeks prior to neurological symptom onset
**Campylobacter most common, also CMV, EBV, myocoplasma, haemophilus, hepatitis E, ZIKA, COVID
Less common = non infectious triggers -> surgical, vaccination, immunosupression, pregnancy (risk of GBS higher with influenza than with influenza vaccines).
If GBS within 6-8 weeks of any vaccine -> recommend that the vaccine not be given again
Neurological nadir reached within 4 weeks (usually 2 weeks)
Recovery usually beings within 2-4 weeks of the nadir
GBS
Pathology and pathogenesis
- **AIDP, AMAN and AMSAN - common pathological features
- **Complement activation
- Upregulation of Fc receptors for IgG
- Macrophage induced contact dependent injury. Schwann cell/myelin injury (AIDP), axon injury (AMAN/ASMAN)
- **acute autoimmune disorder triggered by environmental agents in genetically susceptible individuals
- Post-infectious molecular mimicry hypothesis
- **Antiganglioside antibodies considered pathogenetically relevant to AMAN& Miller Fisher syndrome
- Pathological relevance of antiglycan antibodes in AIDP is questionable
Notes on AIDP
- Most common - up to 90%
- Initial symptoms - sensory or pain (radicular, back pain, paraesthesia) usually without sensory examination findings
- Predominantly motor polyradiculopathy with acute progressive symmetric weakness involving proximal and distal muscles - classic pattern ascending weakness but can start proximally and be confined to lower limbs
- **Reduced or absent DTRs
- 25-30% respiratory muscle weakness requiring ventilation
- **>50% cranial nerve involvement -> facial weakness, ophthalmoplegia, dysphagia, altered taste
- Dysautonomia in majority with variable severity -> sinus tachy, sinus arrhythmia, labile BP, orthostatic hypotension, abnormal sweating & pupil abnormalities
- Sphincter dysfunction can occur
Notes on AMAN & AMSAN
**AMAN
**<10%, most common axonal form
Higher incidence Asia, Centra & South America
Motor weakness starting in lower limbs, can start in upper limbs or cranial nerves
Loss of reflexes corresponds to severity of weakness
- Sparing of muscle afferent fibres predominantly affected in AIDP
- Reflexes may be normal or increased
Minimal sensory impairment
Autonomic dysfunction less common than with AIDP
Notes on Miller Fisher syndrome and Bickerstaf brainstem encephalitis
**Miller Fisher syndrome
**Triad of ophthalmoplegia, ataxia and areflexia
Often presents with diplopia
Sgnificant proportion do not have the classic triad or have additional features/overlap with classic GBS
**Bickerstaff brainstem encephalitis
**Ophthalmoplegia, ataxia, altered consciousness +/- hyperreflexia
Differential diagnosis for GBS
**Infections affecting anterior horn cells
**West Nile virus, enteroviruses, rabies, polio
**NMJ disorders
**Myasthenic crisis, botulism
**Acute severe myopathies
**Immune-mediated necrotising myopathies, acute myositis, rhabdomyolysis
**Periodic paralysis
Acute/subacute neuropathies & polyradiculopathies
**Inflammatory.immune -> acute onset CIDP, vasculitic, neuropathy, sensory ganlionitis
Critical illness neuropathy
Metabolic -> DM, porphyra
Nutritional - thiamine deficiency
Infection - HIV, herpes viruses (CMV), lyme disease
Toxic - organophosphate, hexacarbons
GBS
Diagnosis & Investigations
- Clinical features most important for diagnosis
- **Investigations
- **CSF - may not be positive in the first week.
- Normal cell counts, elevated protein, protein >80% after the first wek
- Nerve conduction studies and EMG -may not be diagnostic in the first week
- Imaging
GBS
Diagnosis & Investigations
- Clinical features most important for diagnosis
- **Investigations
- CSF - may not be positive in the first week.
- **Normal cell counts, elevated protein, protein >80% after the first wek
- Mild increase in WCC in 10-15% (<50)
- IVIG can increase CSF WCC and protein if LP done after treatment commences
**Nerve conduction studies and EMG -may not be diagnostic in the first week - Imaging
- Not routine, may be used to exclude differentials
- Gadolinium enhanced MRI -> nerve root enchancement - not specific but sensitive for GBS
- -Peripheral nerve ultrasound -> enlarged cervical nerve roots may be seen early in disease course
Findings on NCS and EMG in GBS
**Early NCS findings
**Normal
Prolonged F waves (or absent responses) reflecting involvement of proximal nerve trunks/roots
AIDP: sural sparing pattern - preserved sural response, upper limb sensory responses absent or reduced amplitude
**Other NCS findings peak at 2 weeks post symptoms and depend on subtype
**AIDP: Prolonged distal motor latencies, reduced motor nerve conduction velocities, prolonged F wave latencies (or absent responses). Decreased compound muscle action potential amplitudes
ASMAN: Decrease compound muscle action potential amplitudes & decreased sensory nerve action potential amplitudes
Antibody tests in GBS
**Miller Fisher
**GQ1b antibodies in 80%
GBS
Management
**General principles slide attached
IVIG & PLEX
**Hasten recovery and equally efficacious
40-50% do not have a clinical respose
Combination treatment discouraged (not evidence for additional benefit)
2nd course of IVIG not beneficial in severe disease - A/W more adverse events including thromboembolic events
Early treatment preferable as may limit endoneurial inflammation & nerve injury
No clear guideline/recommendation of what to do with treatment failure
**IVIG
**Hastens recovery when given within 2 weeks of onset
Considered 1st line
**PLEX
**Evidence for hastening recovery when given up to 4 weeks after onset
GBS
Treatment related fluctuations
**Definition
**Worsening of at least 1 point on the GBS disability scale after initial improvement or stabilisation within 8 weeks of disease onset
Occurs in up to 10% of patients treated with IVIG and PLEX
No evidence based treatment recommendation
General consensus is retreatment with the original treatment
GBS
Outcomes and Prognosis
Monophasic >95%, recurs in <5%
Recovery usually within 2-4 weeks of nadir, can be delayed up to 6 months. Most completly recovery over 6-12 months
Residual deficits -> fatigue, pain, weakness, 20% unable to walk independently
Poor prognostic factors - age > 40 years, preceding diarrhoea, short interval from onset to nadir, mechanical ventilation, high grade neurological deficits on the GBS disability scale, persistently low CMAP amplitudes
Mortality rate 3-7%. Increased risk with advanced age, disease severity, mechanical ventilation, systemic infection , cardiopulmonary complications
Causes of death -> arrest from autonomic disturbance, respiratory failure, respiratory infection, pulmonary embolism
Notes on newer developments in GBS
**Complement inhibitors
**Eculizumab (humanised Ab against C5)
**Neonatal Fc receptor inhibitors
Hypersialylated IVIG
Classification of nerve fibres
**General rules
**Motor = large, myelinated
Sensory - touch, vibration, position -> large, myelinated fibres
Sensory - pain and temp - smaller, less myelinated/unmyelinated fibres
Autonomic - thin, unmyelinated
